Muscle Metabolism BMS 201

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Questions and Answers

Which organ primarily synthesizes creatine?

Brain

Muscle

Liver (correct)

Heart

What is the function of creatine in muscle tissue?

It serves as a primary energy source.

It is reversibly phosphorylated to regenerate ATP. (correct)

It is a structural protein.

It acts as a neurotransmitter.

Which amino acid is essential for the synthesis of creatine?

Tyrosine

Active methionine (correct)

Glutamic acid

Lysine

What does an elevated creatinine level in the plasma indicate?

Impaired kidney function Signup and view all the answers

What is the normal serum creatinine level range for adult males?

0.6 to 1.2 mg/dL Signup and view all the answers

Which isoenzyme of creatine kinase (CK) is primarily found in heart muscle?

CK-MB Signup and view all the answers

What happens to creatinine levels in conditions of muscle atrophy?

Levels decrease in blood and urine. Signup and view all the answers

Where does the process of glycogenesis primarily occur?

Cytoplasm of liver and muscle Signup and view all the answers

What is the primary fuel source used during the first few seconds of intense muscular contraction?

Creatine phosphate Signup and view all the answers

Where does the synthesis of creatine phosphate predominantly occur?

In the kidneys Signup and view all the answers

Which amino acids are necessary for the synthesis of creatine phosphate?

Glycine, Arginine, Methionine Signup and view all the answers

What mechanism is primarily used to replenish ATP during prolonged exercise?

Oxidative phosphorylation Signup and view all the answers

What determines the primary fuel used to support muscle contraction?

Combination of exercise magnitude, duration, and type of muscle fibers Signup and view all the answers

During a short sprint, which energy system is predominantly utilized?

Phosphocreatine system Signup and view all the answers

What is the initial fuel source for muscle contraction during the first few seconds of exercise?

ATP stored in muscle Signup and view all the answers

What is the role of creatine kinase in the phosphocreatine system?

To convert creatine phosphate and ADP to ATP Signup and view all the answers

Which of the following describes the anaerobic glycolysis process during exercise?

Depends on blood glucose or breakdown of muscle glycogen Signup and view all the answers

Which of the following statements is true regarding the glycolytic system?

It involves the breakdown of glycogen into lactate. Signup and view all the answers

What is the role of creatine phosphate in muscle metabolism?

It helps synthesize ATP for muscle contraction Signup and view all the answers

Which type of phosphorylation occurs in the mitochondria and uses oxygen?

Oxidative phosphorylation Signup and view all the answers

Which type of muscle fibers is predominantly active in anaerobic conditions?

Type II fast glycolytic fibers Signup and view all the answers

Which of the following is a clinical significance of creatinine?

Acts as a marker for kidney function Signup and view all the answers

How is glycogen synthesized in muscle tissues?

From excess blood glucose through a series of enzymatic steps Signup and view all the answers

What is the primary reason glycogen is needed in muscles?

For ATP synthesis during prolonged exercise Signup and view all the answers

What covalent change does insulin induce in glycogen phosphorylase?

Dephosphorylation to inactivate it Signup and view all the answers

Which hormone primarily activates glycogen phosphorylase in the liver?

Glucagon Signup and view all the answers

What type of glycogen storage disease is associated with a deficiency in glucose-6-phosphatase?

Von Gierke's disease Signup and view all the answers

Which clinical manifestation is NOT associated with Von Gierke's disease?

Myopathy Signup and view all the answers

What is the main enzyme deficient in Pompe disease?

Lysosomal acid maltase Signup and view all the answers

Which glycogen storage disease is characterized by failure to thrive?

Anderson disease Signup and view all the answers

What condition results from a deficiency of muscle glycogen phosphorylase?

MacArdle disease Signup and view all the answers

Which enzyme deficiency is associated with increased hepatic content of glycogen and TAG?

Hepatic glycogen phosphorylase Signup and view all the answers

What is the glycogen primer composed of?

A stretch of 4-6 glucose molecules Signup and view all the answers

Why is a glycogen primer necessary for glycogenesis?

Glycogen synthase cannot initiate chain synthesis using free glucose. Signup and view all the answers

What role does glycogenin play when glycogen stores are depleted?

It acts as a primer by auto-glucosylating itself. Signup and view all the answers

What is the first step in synthesizing UDP-glucose?

Conversion of glucose to glucose 6 phosphate Signup and view all the answers

Which enzyme is responsible for catalyzing the formation of 1,4 glycosidic bonds in glycogenesis?

Glycogen synthase Signup and view all the answers

What is the significance of branching enzymes during glycogenesis?

They establish branch points in the glycogen structure. Signup and view all the answers

What is a key reason for synthesizing glycogen?

To maintain blood glucose levels during early starvation. Signup and view all the answers

How does glycogen storage reduce osmotic effect of glucose?

By storing glucose as glycogen instead of free glucose. Signup and view all the answers

What is the primary role of glucose 6 phosphatase in the liver during glycogenolysis?

To convert glucose 6 phosphate to free glucose. Signup and view all the answers

Which form of glycogen synthase is considered active?

Glycogen synthase a. Signup and view all the answers

What effect do glucagon and epinephrine have on glycogen synthase?

They inhibit glycogen synthase. Signup and view all the answers

Which of the following molecules allosterically activates glycogen synthase?

Glucose 6 phosphate. Signup and view all the answers

What is the function of glycogen phosphorylase in glycogenolysis?

It breaks down glycogen into glucose 1 phosphate. Signup and view all the answers

Which regulatory hormone is known to covalently activate glycogen synthase?

Insulin. Signup and view all the answers

How does glucose 6 phosphate influence glycogenolysis?

It inhibits glycogen phosphorylase. Signup and view all the answers

Which of the following is an inactive form of glycogen phosphorylase?

Dephosphorylated form. Signup and view all the answers

Study Notes

Course Information

Course Title: Muscle Metabolism
Course Code: BMS 201
Instructor: Dr. Wael Elayat
Institution: GALALA UNIVERSITY
Semester: Spring 2024

Learning Objectives (ILOs)

Identify that muscle uses 3 energy systems.
Describe creatine-phosphate energy system.
Describe synthesis of creatine, creatine-phosphate.
Describe creatinine, degradation product of creatine and its clinical significance.
Recognize CK and its isozymes and their clinical significance.
Describe glycogen.
Realize the need of muscle for glycogen.
Describe steps of glycogen synthesis.
Describe steps of glycogen breakdown.
Explain regulation of glycogen metabolism: allosteric & hormonal.
Relate enzymatic defects in glycogen metabolism to metabolic diseases.

Muscle as a Chemical Transducer

Muscle is the major biochemical transducer converting chemical energy into kinetic/mechanical energy.
Effective transduction requires a constant supply of chemical energy (e.g., ATP in vertebrates).

Muscle Contraction Fuel Sources

The primary fuel for muscle contraction depends on the magnitude and duration of exercise, as well as the type of muscle fibers involved.
Skeletal muscle stores glycogen and some triglycerides.
Blood glucose and free fatty acids can also be used as fuels.

Muscle Fiber Types

Type II (fast, glycolytic, white fibers): Predominantly active in anaerobic conditions.
Type I (slow, oxidative, red fibers): Active in aerobic conditions.

ATP Breakdown in Muscle Contraction

Muscle contraction relies on ATP breakdown to release free energy, which is coupled to energy requirements for contraction.
ATP → ADP + Pi + energy → muscle contraction

ATP Storage in Muscle

The total amount of ATP stored in the body's muscle cells is small (approximately 8 mmol/kg wet weight of muscle).
This amount is sufficient for maximum contraction for only about 4 seconds.
Muscles rely on replenishing ATP stores.

Importance of ATP Store

ATP stores are sufficient for activity for hours.
Muscle activity depends on ATP for its activity.

ATP Stores and Regeneration

Initial ATP stores in muscle are depleted within the first 4 seconds of exercise.
ATP is regenerated via direct phosphorylation with creatine phosphate.
This phase lasts about 10 seconds
Anaerobic glycolysis from blood glucose or glycogen provides ATP for 1-2 minutes of prolonged exercise.
Aerobic pathways using free fatty acids and glucose provide ATP for hours of prolonged exercise.

Mechanisms for ATP Replenishment

ATP phosphocreatine system (anaerobic)
Glycolytic system (anaerobic)
Oxidative phosphorylation (aerobic)

In-class Assessment Question

Which of the following is a fuel source of energy in the absence of oxygen?
- Glycogen or glucose

Creatine Phosphate Metabolism (Anabolism)

Creatine phosphate is a high-energy molecule found in muscle.
It maintains intracellular ATP levels during intense exercise.
It primarily dominates the first few seconds of intense muscle contractions.
The synthesis begins in the kidney and continues in the liver.
Synthesis depends on the health of the kidney and liver.
The amount of creatine phosphate correlates to muscle mass.

Creatine Phosphate Synthesis Requirement

Requires three amino acids: Glycine, Arginine (guanido group of arginine), and methionine.

Creatine Phosphate Fate

Creatine is constantly synthesized daily from the breakdown of creatine and creatine phosphate.
Creatinine diffuses from muscle to the blood to be excreted by the kidneys.
Creatinine levels in urine and blood are directly proportional to total creatine phosphate content in the body and muscle mass.

Clinical Significance of Creatine Metabolism

Creatinine levels in blood and urine are directly proportionate to total creatine phosphate content in the body and muscle mass.
Creatinine can be used as an indicator of kidney function and muscle mass.
High creatinine in plasma indicates impaired kidney function.
Low creatinine levels in blood and urine indicate muscle dystrophy.
Normal serum creatinine levels are 0.6 - 1.2 mg/dL in adult males, and 0.5 - 1.1 mg/dL in adult females.

CK Isoenzymes

CK has three isoenzymes (CK-MM, CK-MB, CK-BB) with different distributions in skeletal, heart, and brain muscle, respectively.
Serum total CK increases with damage to skeletal or cardiac muscles (e.g., myocardial infarction).

Glycogen Metabolism

Glycogenesis (synthesis of glycogen).
- Definition: the storage of excess glucose in a compact form.
- Site: cytosol of liver and muscle cells.
- Steps: involves the glycogen primer formation and chain elongation from UDP glucose.

Glycogen Synthesis Steps

Preparation of a substrate: Glycogen primer (a short chain of glucose residues).
Elongation of glycogen chain: glycogen synthase adds glucose to the primer.
Branching: Branching enzyme creates branches in the glycogen chain.

Glycogen Breakdown (Glycogenolysis)

Steps in glycogen breakdown
- Glycogen phosphorylase and debranching enzymes break down glycogen to glucose-1-phosphate.
- Phosphoglucomutase converts Glucose-1-phosphate into Glucose-6-phosphate.
- Glycogen is utilized to supply energy for muscle contraction in muscles.
- In the liver, glucose-6-phosphate is converted to free glucose to maintain blood glucose levels.

Hormonal Regulation of Glycogen Metabolism

Insulin: primarily promotes glycogen synthesis.
Glucagon: activates glycogen breakdown.
Epinephrine: promotes glycogen breakdown, especially in the liver and muscles.
Adenylate cyclase, cAMP, phosphodiesterase also play a role

Allosteric Regulation of Glycogen Metabolism

Glucose 6-phosphate and ATP allosterically inhibit glycogen breakdown.
Increased intracellular Ca²⁺ activates glycogen phosphorylase.

Inborn Errors of Glycogen Metabolism (Glycogen Storage Diseases)

A group of inherited disorders affecting glycogen metabolism.
Different types are associated with different deficient enzymes.

References

Lippincott Illustrated Review Integrated system
Lippincott Illustrated Review 6th Edition
Oxford Hand book of Medical Science 2nd Edition
Clinical Key Student

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Description

Test your understanding of muscle metabolism in this quiz for the BMS 201 course. Explore key concepts like energy systems, the role of glycogen, and the clinical significance of creatine and its derivatives. Understand the biochemical processes that underlie muscle function and its energy requirements.